Ethacrynic acid inhibits transcellular NaCl reabsorption in dog kidneys in doses of 1 to 10 mg.kg-1 and proximal bicarbonate-dependent reabsorption at higher doses.
In anesthetized dogs, sodium reabsorption in the kidney tubule was continuously reduced with increasing dosage of ethacrynic acid until 59% of the filtered load was excreted with 25 mg.kg-1 at constant glomerular filtration rate. With 50 mg.kg-1, glomerular filtration rate fell, but fractional sodium reabsorption was further reduced by 7%. In the dosage range of 1 to 10 mg.kg-1, ethacrynic acid inhibited chloride but not bicarbonate reabsorption, and the ratio between reductions in sodium reabsorption and oxygen consumption (delta Na/delta O2) averaged 25.5 +/- 5.2. With doses of 25 and 50 mg.kg-1, ethacrynic acid further reduced chloride reabsorption, reduced fractional bicarbonate reabsorption by 17% and almost halved phosphate reabsorption, whereas delta Na/delta O2 rose significantly to 65.3 +/- 12.2. Renal cortical carbonic anhydrase activity was normal and the inhibitory effect of acetazolamide, a carbonic anhydrase inhibitor, on bicarbonate reabsorption was unimpaired. We conclude that ethacrynic acid in doses up to 10 mg.kg-1 exclusively inhibits transcellular NaCl reabsorption, but in higher doses interferes with bicarbonate reabsorption and bicarbonate-dependent passive reabsorption of NaCl in the proximal tubules without inhibiting carbonic anhydrase activity.
D000042:Absorption; D000818:Animals; D001639:Bicarbonates / Q000378:metabolism*; D002256:Carbonic Anhydrases / Q000378:metabolism; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004976:Ethacrynic Acid / Q000494:pharmacology*; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects; D007668:Kidney / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D010101:Oxygen Consumption / Q000187:drug effects; D012965:Sodium Chloride / Q000378:metabolism*
D001639:Bicarbonates; D012965:Sodium Chloride; D002256:Carbonic Anhydrases; D004976:Ethacrynic Acid